Uterotonics
and Tocolytics in
Medical Disorders
How Safe are They?
Nuzhat Aziz
Hyderabad, INDIA
www.fernandezhospital.com
Tocolytics
are drugs used to stop
Uterine contractions
Uterotonics
to INDUCE / INCREASE
uterine contractions
Why do we use them?
 Tocolytics
 Stop preterm labour for 48 hours
 For Corticosteroid effect, in-utero transfer
 In utero resuscitation, ECV
 Uterotonics
 Induction of uterine contractions
 Augmentation of labour
 To prevent / treat PPH
Why do Obstetricians use these?
 Tocolytics
 For in utero resuscitation
 For To
external
cephalic
improve
fetalversion
survival
 Difficult delivery
 Uterotonics
 Miscarriage
Important - maternal survival
Why should we have this session?
 Medical disorders complicating pregnancy
 Altered hemodynamics
 May not withstand changes
 Effects of smooth muscle
 Bronchospasm
 Patient safety measure
 Effects of uterotonics / tocolytics
Smooth Muscles
We want to either relax
or contract the uterine
muscle
Smooth Muscles
Other parts of the body
We get GI disturbances
Affects heart contractility
Bronchial muscles
Smooth Muscles
Other parts of the body
Pulmonary arteries / veins
Pulmonary vascular resistance
Systemic circulation
Systemic vascular resistance
Coronary arteries
Angina, Ischemia
Brain
Vasospasm, strokes
What is the recommended drug?
Beta-mimetics
Ritodrine
Isoxsuprine
Terbutaline
Magnesium sulphate
Calcium channel blockers
Nifedipine
Prostaglandin inhibitors
Indomethacin
Oxytocin receptor antagonist Atosiban
Very Important to Remember
They are of benefit only for short time tocolysis
No LONG
Term
Therapy
Tocolytic treatment for the management of preterm labour:
a systematic review. Tan et al. Singapore Med J 2006; 47(5) : 364
Why are we
worried about using them in
Medical Disorders ?
Beta-mimetics Drugs
Terbutaline
Hemodynamic Changes
Myocardial
Heart Rate O2 demand
Myocardial
Fatigue
Vascular
Resistance
Beta-mimetics
Contraindications





Cardiac disease
Hyperthyroidism
Chorioamnionitis
Maternal tachycardia
Sepsis
Beta-mimetics Drugs
Lactic Acidosis
 Glycogenolysis ↑
 hyperglycemia
 Lactic acid production ↑
 → metabolic acidosis
 Hypokalemia
Lactic Acidosis: Recognition, Kinetics, and Associated Prognosis.
Crit Care Clin 26 (2010) 255–283
Beta-mimetics
Contraindications





Cardiac disease
Hyperthyroidism
Chorioamnionitis
Maternal tachycardia
Sepsis
 Poorly controlled
diabetes
Pulmonary Edema, Maternal Deaths
Beta-mimetics





Incidence of pulmonary edema – 4%
Non cardiogenic
Multiple tocolytics
Fluid overload
Multifactorial
Predisposing Risk Factors for
Pulmonary Edema




Heart disease
Pregnancy induced HTN
Chorio-amnionitis
Sepsis, Infections
Betamimetics +
Corticosteroids + IV fluids
Terbutaline
Not for prolonged treatment / No Oral use
Oral Nifedipine




Effective smooth muscle dilator
Lesser maternal effects
Better tocolytic
Contraindicated in
 Cardiac disease, aortic stenosis
 Hypotension
Sublingual Nifedipine
 Increased adverse effects
 Systemic vasodilation
 Early, profound
 Delayed response on heart
 Angina, Reflex tachycardia
 Increased MORTALITY
Indomethacin




Before 32 weeks
Loading Dose: 50 mg
Maintenance 25 mg 4th hourly for 48 hours
Contraindications:
 Maternal Hepatic or renal disease
 Acid peptic disease
 Oligohydramnios
Basic Rules for use of Tocolytics




They are used for short time – 48 hours
Calcium channel blockers preferred
Indomethacin before 32 weeks
Do not give:
 Cardiac disease, hypotension, critically ill mother
 Fetal distress, chorioamnionitis, abruption
Avoid Complications
 Do not give tocolytics if
 Maternal tachycardia - > 120 bpm
 Cardiac disease, infection
 Be careful with IV fluid infusion
 Do not use multiple drugs
 WATCH OUT for pulmonary edema
How Safe are they?
 Absolute
 Acute vaginal bleeding
Fetal distress
Lethal fetal anomaly
Chorioamnionitis
Preeclampsia or eclampsia
Sepsis
DIC
 Relative
 Chronic hypertension
Cardiopulmonary disease
Stable placenta previa
Cervical dilation >5 cm
Placental abruption
All
contraindications
have to be
honoured
Uterotonics
and
Medical Disorders
Uterotonics
 1. Oxytocin
 2. Prostaglandins
 Misoprostol (Cytotec)
 15-methyl Prostaglandin F2!
 3. Ergot Alkaloids
 Methylergonovine (Methergine)
Uterine
Contraction causes
Auto-transfusion
Uterine Blood
into
Systemic Circulation
Cardiac Output
15% in I stage
50% in II stage
Uterotonics
effect
smooth muscle
function
Uterotonics
have an important role in
prevention and
management of PPH
Medical Diseases and Uterotonic Agents
Cardiac Disease
Pre-eclampsia
Asthma
Vascular diseases
Oxytocin




Prophylaxis & treatment of atonic PPH
IM : 10 units as prophylaxis
At Cesarean : 3 - 5 units IV bolus
Hemodynamic changes
 IV bolus > IV infusion > IM dose
Hemodynamic changes
OXYTOCIN
 Dose dependent
 3 units - 5 units – 10 units
 One bolus Vs 2 bolus
Increases heart rate
Decreases contractility
Decreases SVR significantly
Changes with
5 U Oxytocin
Oxytocin
 Hypotension
 Chest pain
 ECG changes
Svanström. Signs of myocardial ischaemia after
injection of oxytocin: a randomized double-blind
comparison of oxytocin and methylergometrine
during Caesarean section.
Br J Anaesth 100:683–689
Oxytocin
Take home message
 IV infusion or IM use preferred
 IV bolus at cesarean section:
 3 or 5 IU
 IV infusion:
 Dose dependent effects - TITRATE
Prostaglandins
 Endogenous prostaglandins in labour
 Peak at placenta delivery
 Action by increasing calcium
 Prostaglandins E : Misoprostol
 F classes : Carboprost tromethamine
Misoprostol in Cardiac Disease
 Misoprostol PGE1
 Best uterotonic to use in postpartum period
 800 microgram, per rectal / oral
 Antepartum period
 Dinoprostone PGE2
 Lesser incidence of hyperstimulation
PGF 2 alpha, Carboprost






For PPH
Dose : 250 mcg IM
Maximum of 8 doses at 15 min interval
Can be given intramyometrial
Increases pulmonary vascular resistance
Contraindicated in PAH, Asthma
Methyl ergometrine





Potent uterotonic drug
Increases BP
Intense vasospasm : angina, strokes
Exaggerated response: pre eclampsia
IV cause more hemodynamic changes.
Medical Disorders and Uterotonics
How can we
make the safe?
Cardiac Disease and Uterotonics
 Ask yourself





Is there PAH?
Will this patient tolerate increased HR?
Can she tolerate fall in cardiac contractility ?
Does she have a tight valvular lesion ?
Can she tolerate fall in systemic vascular resistance ?
CARPREG Score
Prior cardiac events
1
Heart failure, TIA, stroke before pregnancy
Prior arrhythmia
NYHA III or IV or cyanosis
Valvular and outflow tract obstruction
1
1
1
Aortic v area < 1.5 cm2, mitral v area < 2 cm2,
Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction
LVEF < 40%, Cardiomyopathy
1
CARPREG Score
Prior cardiac events
1
Heart failure, TIA, stroke before pregnancy
Prior arrhythmia
NYHA III or IV or cyanosis
Valvular and outflow tract obstruction
1
1
1
Aortic v area < 1.5 cm2, mitral v area < 2 cm2,
Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction
LVEF < 40%, Cardiomyopathy
1
Cardiac disease
Severe Valvular Heart Disease
20 units in 500 ml
 Prophylaxis
at 125 ml/hour
 Oxytocin
(4 hours)– IM or infusion only
 Misoprostol as a second line
Cardiac
Disease
 Restrict IV fluids
Use a syringe pump
20 units in 20 cc syringe
5 U per hour for 4 hours
Cardiac disease
Severe Valvular Heart Disease
without PAH
 Life threatening hemorrhage
 PGF2α : watching for its effects
 Methyl ergometrine
Cardiac disease
Decreased Ejection Fraction
 PPCM, Cardiomyopathy
 Oxytocin may cause sudden hypotension
 IV infusion
 Being prepared to tackle a crisis
 Second drug of choice - Misoprostol
Cardiac disease
Increased Pulmonary HTN
 Primary / secondary
 Avoid PGF2 alpha
 Intense pulmonary vascular constriction
 Increases PAH
 Shunt reversal
 Methyl Ergometrine : before PGF2 alpha
Asthma
 Prostaglandin F class
 Bronchospasm
 Pulm vasoconstriction
 History Vs acute episode
 Tackle bronchospasm
1
Oxytocin
2
3
Methergine
Carboprost
Moderate to High Risk Lesions
NYHA III or IV
Invasive hemodynamic monitoring
Aneasthetist / intensivist / cardiologist
Know the effects
Be prepared to tackle the effects
Cardiac Disease
Order of use
 Oxytocin
 20 units infusion
 Titrate to effect
 Misoprostol
 800 µg rectal / oral
Life threatening PPH
 PGF2α
 Do not use in PAH, shunts
 Methergine
 Do not use in CAD, PE,
aneurysms
ABC of resuscitation
Uterotonics
are life saving
drugs
Part of PPH protocol
Relative contraindications
Bimanual compression
Uterotonics
Tamponade
Compression sutures
Hysterectomy
Conclusions
Tocolytics : Making them Safer
 Isoxsuprine / Ritodrine : Not to be used
 Terbutaline for rapid action : not available
 Do not use multiple drugs
 Do not give in CARDIAC disease / infection
Conclusions
Uterotonics : Life Saving Drugs
 IV bolus Oxytocin : not to be given
 Tertiary care centre : multidisciplinary
 Carboprost increases PAH
 Oxytocin and cardiomyopathy
 Medical disorders : relative contraindications